Rifaximin (INN; see The Merck Index, XIII Ed., 8304), an antibiotic belonging to the rifamycin class, is a pyrido-imidazo rifamycin described and claimed in Italian Patent IT 1154655. European Patent EP 0161534 describes a process for its production starting from rifamycin O (The Merck Index, XIII Ed., 8301). Methods for making polymorphic forms of rifaximin are described in U.S. Patent Application Publication 2008-0262232, by Viscomi et al., which is incorporated by reference herein in its entirety.
Rifaximin has been used for treating acute and chronic intestinal infections from gram-positive and gram-negative bacteria and as adjuvant in the therapy of the hyperammonoaemia. Rifaximin is marketed in the United States as XIFAXAN™ for the treatment of travelers' diarrhea caused by the noninvasive strains of Escherichia coli. Rifaximin has also been used to treat Clostridium difficile-associated diarrhea, Crohn's disease, diverticular disease, hepatic encephalopathy, Helicobacter pylori eradication, infectious diarrhea, irritable bowel syndrome, pouchitis, prophylaxis for GI surgery, small bowel overgrowth, traveler's diarrhea and ulcerative colitis. Rifamycin derivatives bearing a heterocyclic ring condensed at the 3,4-position are known in the art. For example, U.S. Pat. Nos. 4,263,404 and 4,341,785 describe rifamycin and imidazo-rifamycin derivatives. Rifamycins have antibacterial activity and they are obtained from secondary metabolites of micro-organism cultures, useful in the treatment of infections, in particular in the tuberculosis as described by Sensi P. in Farmaco [Sci], (1959); 14:146-7 and by Mitnick C. D. et al. in Expert Opin. Pharmacother. (2009); 10:381-401. Recently the rifamycin derivatives have been identified as activators of the receptor X of pregnane (PRX), a member of the family of the nuclear receptor that regulates the metabolic enzyme expression involved in the mammalian response to chemical stimulation, as described Natl. Acad. Sci. USA, (1998), 95: 12208-12213.
Rifamycins are characterized by a chemical structure constituted from one or more condensed aromatic rings, forming a cyclic structure with an aliphatic ring as described by Prelong, V. et al. in Helv. Chim. Acta (1973); 56:2279. Rifamycin analogues are obtained by a chemical modification of the aromatic or aliphatic portions of the molecule, as described by Sensi P. in Research Progress in Organic Biological and Medicinal Chemistry (1964), 1, 337-421.